crossing96/oncoscreening huggingface dataset:
The Clinical Research Office of the Endourological Society (CROES) Multicentre Randomised Trial of Narrow Band Imaging-Assisted Transurethral Resection of Bladder Tumour (TURBT) Versus Conventional White Light Imaging-Assisted TURBT in Primary Non-Muscle-invasive Bladder Cancer Patients: Trial Protocol and 1-year Results.	BACKGROUND: White light (WL) is the established imaging modality for transurethral resection of bladder tumour (TURBT). Narrow band imaging (NBI) is a promising addition. OBJECTIVES: To compare 12-mo recurrence rates following TURBT using NBI versus WL guidance. DESIGN, SETTING, AND PARTICIPANTS: The Clinical Research Office of the Endourological Society (CROES) conducted a prospective randomised single-blind multicentre study. Patients with primary non-muscle-invasive bladder cancer (NMIBC) were randomly assigned 1:1 to TURBT guided by NBI or WL. INTERVENTION: TURBT for NMIBC using NBI or WL. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Twelve-month recurrence rates were compared by chi-square tests and survival analyses. RESULTS AND LIMITATIONS: Of the 965 patients enrolled in the study, 481 patients underwent WL-assisted TURBT and 484 patients received NBI-assisted TURBT. Of these, 294 and 303 patients, respectively, completed 12-mo follow-up, with recurrence rates of 27.1% and 25.4%, respectively (p=0.585, intention-to-treat [ITT] analysis). In patients at low risk for disease recurrence, recurrence rates at 12 mo were significantly higher in the WL group compared with the NBI group (27.3% vs 5.6%; p=0.002, ITT analysis). Although TURBT took longer on average with NBI plus WL compared with WL alone (38.1 vs 35.0min, p=0.039, ITT; 39.1 vs 35.7min, p=0.047, per protocol [PP] analysis), lesions were significantly more often visible with NBI than with WL (p=0.033). Frequency and severity of adverse events were similar in both treatment groups. Possible limitations were lack of uniformity of surgical resection, data on smoking status, central pathology review, and specific data regarding adjuvant intravesical instillation therapy. CONCLUSIONS: NBI and WL guidance achieved similar overall recurrence rates 12 mo after TURBT in patients with NMIBC. NBI-assisted TURBT significantly reduced the likelihood of disease recurrence in low-risk patients. PATIENT SUMMARY: Use of a narrow band imaging technique might provide greater detection of bladder tumours and subsequent treatment leading to reduced recurrence in low-risk patients.	bladder
Prediction of Lymph Node Metastasis in Patients with Bladder Cancer Using Whole Transcriptome Gene Expression Signatures.	PURPOSE: Clinical staging in patients with muscle invasive bladder cancer misses up to 25% of lymph node metastasis. These patients are at high risk for disease recurrence and improved clinical staging is critical to guide management. MATERIALS AND METHODS: Whole transcriptome expression profiles were generated in 199 patients who underwent radical cystectomy and extended pelvic lymph node dissection. The cohort was divided randomly into a discovery set of 133 patients and a validation set of 66. In the discovery set features were identified and modeled in a KNN51 (K-nearest neighbor classifier 51) to predict pathological lymph node metastases. Two previously described bladder cancer gene signatures, including RF15 (15-gene cancer recurrence signature) and LN20 (20-gene lymph node signature), were also modeled in the discovery set for comparison. The AUC and the OR were used to compare the performance of these signatures. RESULTS: In the validation set KNN51 achieved an AUC of 0.82 (range 0.71-0.93) to predict lymph node positive cases. It significantly outperformed RF15 and LN20, which had an AUC of 0.62 (range 0.47-0.76) and 0.46 (range 0.32-0.60), respectively. Only KNN51 showed significant odds of predicting LN metastasis with an OR of 2.65 (range 1.68-4.67) for every 10% increase in score (p <0.001). RF15 and LN20 had a nonsignificant OR of 1.21 (range 0.97-1.54) and 1.39 (range 0.52-3.77), respectively. CONCLUSIONS: The new KNN51 signature was superior to previously described gene signatures for predicting lymph node metastasis. If validated prospectively in transurethral resection of bladder tumor samples, KNN51 could be used to guide patients at high risk to early multimodal therapy.	bladder
Improvement and enhancement of antibladder carcinoma cell effects of heteronemin by the nanosized hyaluronan aggregation.	The effects against tumors exerted by marine active compounds have been highlighted and investigated. Polymeric nanoparticles made from biodegradable and biocompatible molecules such as hyaluronan (HA) and chitosan (CHI) are able to aggregate the compounds to enhance their activities against tumor cells and reduce the toxicity on normal cells. Here, we extensively examined the antitumor activities and the mechanisms of HA/CHI nanoparticles-aggregated heteronemin (HET) extracted from the sponge Hippospongia sp. The half-maximal inhibitory concentration (IC50) of pure HET toward T24 bladder carcinoma cells is ~0.28 µg/mL. Pure HET from 0.2 to 0.8 µg/mL and HA nanoparticles-aggregated HET at 0.1 and 0.2 µg/mL significantly reduced T24 cell viability. Compared to pure HET, HA nanoparticles/HET aggregates showed much weaker viability-inhibitory effects on L929 normal fibroblasts. HET dose-dependently suppressed cancer cell migration as HA/CHI nanoparticles-aggregated HET displayed stronger migration-inhibitory effects than pure HET. Flow cytometric analysis showed that pure HET increased early/total apoptosis and JC-1 monomer fluorescence, while HA/CHI nanoparticles-aggregated HET induced higher apoptosis and JC-1 monomer rates than pure HET, suggesting that aggregation of HA nanoparticles offers HET stronger apoptosis-inducing capacity through mitochondrial depolarization. Western blot analysis showed that HA nanoparticles-aggregated HET further increased mitochondrial-associated, caspase-dependent and caspase-independent, as well as endoplasmic reticulum stress-related factors in comparison with pure HET. These data indicated that pure HET possesses cytotoxic, antimigratory, and apoptosis-inducing effects on bladder cancer cells in vitro, and its induction of apoptosis in bladder carcinoma cells is mainly caspase dependent. Moreover, HA nanoparticle aggregation reinforced the cytotoxic, antimigratory, and apoptosis-inducing activities against bladder carcinoma cells and attenuated the viability-inhibitory effects on normal fibroblasts. This aggregation reinforces antibladder carcinoma effects of HET via diverse routes, including mitochondrial-related/caspase-dependent, caspase-independent, and endoplasmic reticulum stress-related pathways. The current data also strongly suggested that HA/CHI nanoparticles-aggregated HET would be a potential treatment for urothelial cancer in vivo.	bladder
Risk of Alcohol Consumption in Bladder Cancer: Case-Control Study from a Nationwide Inpatient Database in Japan.	Bladder cancer is common in Western countries, but not in Japan. Established risk factors are smoking and high-risk jobs such as printing and manufacturing. The risk of alcohol consumption in bladder cancer has been the recent focus; however, available literature on alcohol consumption and bladder cancer has been limited from Japanese population, thought to have a weak genetic tolerance to acetaldehyde. We aimed to determine whether alcohol consumption is an independent risk factor for bladder cancer among Japanese. The study was a matched case-control study from the nationwide Japanese clinical database administered by the Rosai Hospital group. We identified 739 cases of bladder cancer diagnosed between 2005 (when the database was established) and 2014 and 7,196 controls matched by sex, age, hospital, and admission period. We estimated the odds ratio of alcohol consumption for bladder cancer adjusted for the amount of smoking, high-risk occupations, and comorbidities (hypertension, hyperlipidemia, diabetes, hyperuricemia, and obesity) with conditional logistic regression. The risk of bladder cancer was significantly higher in ever drinkers than in never drinkers (odds ratio, 1.33; 95% confidence interval, 1.06 to 1.66). Furthermore, the risk threshold for alcohol consumption was more than 15 g of alcohol intake per day (one, 180-mL cup equivalent to 6 ounces of Japanese sake containing 23 grams of alcohol). Among Japanese, alcohol consumption may be an independent risk factor for bladder cancer, with a lower risk threshold.	bladder
Inhibition of PHLPP2/cyclin D1 protein translation contributes to the tumor suppressive effect of NFκB2 (p100).	Although the precursor protein of NFκB2 (p100) is thought to act as a tumor suppressor in mammalian cells, the molecular mechanism of its anti-tumor activity is far from clear. Here, we are, for the first time, to report that p100 protein expression was dramatically decreased in bladder cancers of N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-treated mice and human patients. Knockdown of p100 in cultured human bladder cancer cells promoted anchorage-independent growth accompanied with elevating abundance of cell-cycle-related proteins and accelerated cell-cycle progression. Above effects could be completely reversed by ectopically expression of p100, but not p52. Mechanistically, p100 inhibited Cyclin D1 protein translation by activating the transcription of LARP7 and its hosted miR-302d, which could directly bind to 3'-UTR of cyclin d1 mRNA and inhibited its protein translation. Furthermore, p100 suppressed the expression of PHLPP2 (PH domain and leucine-rich repeat protein phosphatases 2), thus promoting CREB phosphorylation at Ser133 and subsequently leading to miR-302d transcription. Taken together, our studies not only for the first time establish p100 as a key tumor suppressor of bladder cancer growth, but also identify a novel molecular cascade of PHLPP2/CREB/miR-302d that mediates the tumor suppressive function of p100.	bladder
Short term complications from transurethral resection of bladder tumor.	INTRODUCTION: The diagnosis and subsequent management of bladder cancer often involves transurethral resection of bladder tumor (TURBT). Risks of TURBT include perioperative complications such as bleeding, pain and perforation. We aimed to determine TURBT complication rates and risk factors in a contemporary series. MATERIALS AND METHODS: From 2002 to 2011, 505 patients underwent TURBT either for suspected bladder cancer or during follow up at a single institution. Baseline patient characteristics and complications within 2 weeks of surgery were extracted from the electronic medical record for all TURBTs. Patient and tumor characteristics were evaluated for associations with complication using univariate analysis. A multivariable logistic regression was fit to further examine associations between TURBT related characteristics and complication. RESULTS: A total of 910 TURBTs were performed on 505 patients. Overall complication rate was 8.1%. The most common complications were pain or spasm (3.0%), retention (2.8%), and infection (2.1%), and 0.5% of TURBTs had perforation. Over 85% of complications were Clavien-Dindo grade I or II. Forty-three patients had a complication after their first TURBT, while 25 had complications after subsequent TURBTs. Prior complication and single tumor, but not other patient or tumor-related characteristics, were associated with complication. Only prior complication (p < 0.01) was associated with subsequent complication after TURBT on multivariable analysis. CONCLUSIONS: Complication rate after TURBT is 8.1% and complications are generally not severe in nature. Prior short term complication is likely associated with subsequent complication. Further studies are needed to validate these results and determine patient groups most at risk for intraoperative and post TURBT complications.	bladder
Intravesical Bacillus Calmette-Guérin Versus Combination of Epirubicin and Interferon-α2a in Reducing Recurrence of Non-Muscle-invasive Bladder Carcinoma: FinnBladder-6 Study.	BACKGROUND: Patients with non-muscle-invasive bladder cancer (NMIBC) belonging to the intermediate-risk group should be treated with intravesical instillations to prevent recurrence and progression. OBJECTIVE: We compared the outcome of a monthly maintenance bacillus Calmette-Guérin (BCG) regimen with that of epirubicin (EPI) and interferon-α2a (IFN) in patients with NMIBC. DESIGN, SETTING, AND PARTICIPANTS: Our prospective randomized multicenter study comprised 229 eligible patients with frequently recurrent TaT1 grade 1-2 or low-grade NMIBC enrolled between 1997 and 2008. INTERVENTIONS: The four-arm study involved a single perioperative instillation of EPI plus five weekly instillations of BCG or EPI/IFN, followed by 11 monthly instillations in the 1-yr BCG or EPI/IFN maintenance arms, further followed by four additional quarterly instillations in the two 2-yr maintenance arms. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Time to recurrence, progression, disease-specific survival, and overall mortality were analyzed using the Kaplan-Meier and cumulative incidence analyses plus the Cox and proportional subdistribution hazards models. RESULTS AND LIMITATIONS: The median follow-up time was 7.5 and 7.4 yr in the BCG and EPI/IFN groups, respectively. The probability of recurrence was significantly lower in the BCG group than in the EPI/IFN group. The probability was 39% versus 72% at 7.4 yr, respectively (hazard ratio [HR]: 0.41; 95% confidence interval [CI], 0.28-0.60; p<0.001). There was no significant difference in the probability of progression or in overall survival. However, there was a significant difference in disease-specific mortality in favor of the BCG group (HR: 0.20; 95% CI, 0.04-0.91; p=0.04). CONCLUSIONS: The monthly maintenance BCG regimen showed excellent efficacy and was significantly better in preventing recurrence than a similar regimen of EPI/IFN-α2a. PATIENT SUMMARY: A monthly bacillus Calmette-Guérin (BCG) regimen showed excellent efficacy and was significantly better in preventing recurrence than a similar regimen of epirubicin and interferon-α2a. TRIAL REGISTRATION: Registration was not considered necessary at this stage of the follow-up because the study was initiated as early as in 1997, before the current requirements concerning study registrations were implemented.	bladder
Silencing of RTKN2 by siRNA suppresses proliferation, and induces G1 arrest and apoptosis in human bladder cancer cells.	Human bladder cancer is the most common urological malignancy in China. One of the causes of carcinogenesis in the cancer may be gene mutation. Therefore, the present study investigated the expression levels of Rhotekin 2 (RTKN2), a Rho effector protein, in human bladder cancer tissues and cell lines, and examined the effect of RTKN2 on the proliferation, cell cycle, apoptosis and invasion of human bladder cancer cell lines. The mRNA expression levels of RTKN2 in 30 human bladder cancer tissue samples were significantly higher, compared with those in 30 normal human bladder tissue samples. The protein expression levels of RTKN2 was markedly higher in T24 and 5637 cells, compared with those in four other human bladder cancer cell lines. The silencing of RTKN2 by small interfering (si)RNA inhibited cell proliferation and arrested cell cycle at the G1 phase, via reducing the expression levels of the MCM10, CDK2, CDC24A and CDC6 cell cycle‑associated proteins in the T24 and 5637 cells. Furthermore, RTKN2 knockdown in the cells led to cell apoptosis and the suppression of invasion. These results suggested that RTKN2 is involved in the carcinogenesis and progression of human bladder cancer, indicating that RTKN2 may be a molecular target in cancer therapy.	bladder
Isorhapontigenin (ISO) Inhibits Invasive Bladder Cancer Formation In Vivo and Human Bladder Cancer Invasion In Vitro by Targeting STAT1/FOXO1 Axis.	Although our most recent studies have identified Isorhapontigenin (ISO), a novel derivative of stilbene that isolated from a Chinese herb Gnetum cleistostachyum, for its inhibition of human bladder cancer growth, nothing is known whether ISO possesses an inhibitory effect on bladder cancer invasion. Thus, we addressed this important question in current study and discovered that ISO treatment could inhibit mouse-invasive bladder cancer development following bladder carcinogen N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) exposure in vivo We also found that ISO suppressed human bladder cancer cell invasion accompanied by upregulation of the forkhead box class O 1 (FOXO1) mRNA transcription in vitro Accordingly, FOXO1 was profoundly downregulated in human bladder cancer tissues and was negatively correlated with bladder cancer invasion. Forced expression of FOXO1 specifically suppressed high-grade human bladder cancer cell invasion, whereas knockdown of FOXO1 promoted noninvasive bladder cancer cells becoming invasive bladder cancer cells. Moreover, knockout of FOXO1 significantly increased bladder cancer cell invasion and abolished the ISO inhibition of invasion in human bladder cancer cells. Further studies showed that the inhibition of Signal transducer and activator of transcription 1 (STAT1) phosphorylation at Tyr701 was crucial for ISO upregulation of FOXO1 transcription. Furthermore, this study revealed that metalloproteinase-2 (MMP-2) was a FOXO1 downstream effector, which was also supported by data obtained from mouse model of ISO inhibition BBN-induced mouse-invasive bladder cancer formation. These findings not only provide a novel insight into the understanding of mechanism of bladder cancer's propensity to invasion, but also identify a new role and mechanisms underlying the natural compound ISO that specifically suppresses such bladder cancer invasion through targeting the STAT1-FOXO1-MMP-2 axis. Cancer Prev Res; 9(7); 567-80. ©2016 AACR.	bladder
Challenges with in vitro and in vivo experimental models of urinary bladder cancer for novel drug discovery.	INTRODUCTION: Urinary bladder cancer (UBC) is the second most frequent malignancy of the urinary system and the ninth most common cancer worldwide, affecting individuals over the age of 65. Several investigations have embarked on advancing knowledge of the mechanisms underlying urothelial carcinogenesis, understanding the mechanisms of antineoplastic drugs resistance and discovering new antineoplastic drugs. In vitro and in vivo models are crucial for providing additional insights into the mechanisms of urothelial carcinogenesis. With these models, various molecular pathways involved in urothelial carcinogenesis have been discovered, allowing therapeutic manipulation. AREAS COVERED: This paper provides critical information on existing in vitro and in vivo models to screen the efficacy and toxicity of innovative UBC therapies and point out the challenges for new and improved models. EXPERT OPINION: In our opinion, results obtained with in vitro and in vivo models should be interpreted together, as a set of delicate biological tools that can be used at different stages in the drug discovery process, to address specific questions. With the development of new technologies, new assays and biomarkers are going to play an important role in the study of UBC. The molecular diagnostics and genomic revolution will not only help to develop new drug therapies, but also to achieve tailored therapies.	bladder
Low expression of protocadherin7 (PCDH7) is a potential prognostic biomarker for primary non-muscle invasive bladder cancer.	Bladder cancer is a heterogeneous disease with outcome difficult to predict, and novel predictive biomarkers are needed. PCDH7, a member of protocadherins family, functions as tumor suppressor in several human cancers. The human PCDH7 gene is localized in chromosome 4p15, which is often inactivated in human cancers, including bladder cancer. The aim of this study was to investigate the clinical significance of PCDH7 expression in non-muscle invasive bladder cancer (NMIBC). PCDH7 expression was examined using immunohistochemical staining in 199 primary NMIBC tissues and 25 normal bladder epithelial tissues. Then the relationship between PCDH7 expression and clinicopathologic features was evaluated. Kaplan-Meier survival analysis and Cox analysis was used to evaluate the correlation between PCDH7 expression and prognosis. PCDH7 expression in NMIBC tissues was significantly lower than that in normal bladder epithelial tissues (P < 0.001). Low PCDH7 expression correlated with advanced grade (P = 0.021) and larger tumor size (P = 0.044). Moreover, patients with low PCDH7 expression have shorter recurrence-free survival (P < 0.001), progression-free survival (P = 0.007) and overall survival (P = 0.011) than patients with high PCDH7 expression. Low PCDH7 expression is an independent predictor of recurrence-free survival (multivariate Cox analysis: P = 0.007), progression-free survival (multivariate Cox analysis: P = 0.014) and overall survival (multivariate Cox analysis: P = 0.004). The findings indicate that low PCDH7 expression is a potential prognostic biomarker for primary NMIBC.	bladder
Deregulation of seven CpG island-harboring miRNAs in bladder cancer: miR-155 and miR-23b as the most promising oncomiRs.	Analyses of differential miRNA expressions in tumor and normal tissues can identify specific miRNAs involved in cancer pathogenesis, which can then be used as diagnostic, therapeutic and prognostic biomarkers. In this respect, we aimed to investigate expression levels of seven CpG island-harboring miRNAs in 50 paired UBC tissues by qRT-PCR. miR-21 and miR-155 were found to be significantly upregulated, and miR-23b, miR-126, miR-129-5p, miR-143a and miR-218-5p were downregulated. ROC analysis indicated miR-155 as the most promising candidate for discrimination of tumors from healthy tissue, and miR-23b for the discrimination of early stage from late stage tumors.	bladder
Rapid assessment of drug resistance of cancer cells to gefitinib and carboplatin using optical imaging.	The overall goal of this study was to evaluate optical molecular imaging approaches to determine the drug response of chemotherapy and molecular targeted agents in drug sensitive and drug resistant cell lines. The optical molecular imaging approaches selected in this study were based on changes in intracellular uptake and retention of choline and glucose molecules. The breast cancer cell lines were treated with a molecular targeted anti-EGFR therapy. The bladder cancer cell lines were treated with a conventional chemotherapy approach. Sensitivity of optical molecular imaging approach was also compared with conventional cell viability and cell growth inhibition assays. Results demonstrate that optical molecular imaging of changes in intracellular uptake of metabolites was effective in detecting drug susceptibility for both molecular targeted therapy in breast cancer cells and chemotherapy in bladder cancer cells. Between the selected metabolites for optical molecular imaging, changes in glucose metabolic activity showed higher sensitivity in discrimination between the drug sensitive and drug resistant cell lines. The results demonstrated that optical molecular imaging approaches more significantly sensitive as compared to the conventional cell viability and growth assays. Overall, the results demonstrate potential of optical molecular imaging of metabolic activity to improve sensitivity of in-vitro drug response assays.	bladder